In cerebrospinal fluid acetylcholinesterase activity and somatostatin and neuropeptide Y concentrations did not differ from control values in either young or old Down patients. Analysis of lumbar cerebrospinal fluid fractions in healthy young and old subjects indicated no anterior- posterior gradients for somatostation and neuropeptide Y, but higher acetylcholinesterase in caudal as compared to rostral fractions in younger subjects, indicative of sources for this enzyme from the spinal cord. Cerebrospinal fluid acetylcholinesterase activity was reduced in patients with progressive supranuclear palsy, indicating a central cholinergic deficit. There was no effect on activity of administered physostigmine, and anticholinesterase. Acetylcholinesterase gradients in cerebrospinal fluid were negative in the rostrocaudal direction in young healthy subjects, but were absent in old healthy subjects, who had higher mean activity overall.